Chemotherapy resistance in cancer treatment tied to nearby proteins

(CBS News) Treating cancer patients with chemotherapy may eventually lead to worse cancers coming back once people become resistant to treatment, and scientists now think they’ve discovered why.

Almost all patients develop resistance to chemotherapy, according to the authors behind the new research, and it’s ultimately a deadly consequence for people with cancer that has spread, including those with metastatic breast, prostate, lung and colon cancers.

Researchers at Fred Hutchinson Cancer Center in Seattle set out to discover mechanism of how resistance to chemotherapy occurs, in the hopes that discovering it could open opportunities for more effective treatments.

“Cancer cells inside the body live in a very complex environment or neighborhood, senior author Dr. Peter S. Nelson, a scientist at the center’s human biology division, said in a press release. “Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy.”

By analyzing the genome of cell responses to cancer treatments, the researchers focused on a type of noncancerous, normal cell called the fibroblast that “lives in the cancer’s neighborhood.” Fibroblasts typically play in an important role in wound healing and producing collagen to help maintain structure of cells. When a fibroblast is exposed to chemotherapy, however, its DNA becomes damaged and winds up producing molecules that have been tied to tumor growth.

The researchers observed especially high levels of one molecule in particular, called WNT16B, that enable cancer cells to grow and invade surrounding tissue. When chemotherapy was given to the cells, the researchers observed levels of WNT16B shot up by 30 times, which Nelson called a “completely unexpected” finding. This protein has been eyed in the development of normal cells and even some cancers, but has not previously been identified for its role in tumor resistance.

“Treatments for common solid tumors are given in smaller doses and in cycles, or intervals, to allow the normal cells to recover,” Nelson explained of chemotherapy. “This approach may not eradicate all of the tumor cells, and those that survive can evolve to become resistant to subsequent rounds of anti-cancer therapy.”

“This work confirms that healthy cells surrounding the tumor can also help the tumor to become resistant to treatment,” Professor Fran Balkwill, a professor of cancer biology at Queen Mary University of London who was not involved in the new research, told Cancer Research UK. “The next step is to find ways to target these resistance mechanisms to help make chemotherapy more effective.”

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